Disruption of Tumor Necrosis Factor Receptor Associated Factor 5 Exacerbates Pressure Overload Cardiac Hypertrophy and Fibrosis
Disruption of Tumor Necrosis Factor Receptor Associated Factor 5 Exacerbates Pressure Overload Cardiac Hypertrophy and Fibrosis
复制标题
肿瘤坏死因子受体相关因子 5 的破坏会加剧压力超负荷心脏肥大和纤维化。
DOI：
10.1002/jcb.24669
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发表时间：
2014-02-01
影响因子：
4
通讯作者：
Tang, Qizhu
中科院分区：
文献类型：
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作者：
Bian, Zhouyan;Dai, Jia;Tang, Qizhu
细胞质信号蛋白肿瘤坏死因子（TNF）受体相关因子5（TRAF 5）被鉴定为TNF受体超家族成员的信号转导子，其涉及T/B淋巴细胞中的若干生物学功能和针对病毒感染的先天性免疫应答。然而，TRAF 5在心肌肥大中的作用尚未报道。在本研究中，我们研究了TRAF 5对经胸主动脉缩窄（TAC）诱导的病理性心脏肥大的影响，并进一步探讨了潜在的分子机制。通过超声心动图、血流动力学、病理和分子生物学分析评价心肌肥厚和功能。我们首次发现，与野生型（WT）小鼠相比，TAC治疗4周后，TRAF 5缺乏显着加剧了压力超负荷引起的心脏肥大、心脏功能障碍和纤维化。此外，丝裂原活化蛋白/细胞外信号调节激酶激酶（MEK）-细胞外信号调节激酶1/2（ERK 1/2）信号通路在TRAF 5缺陷小鼠中比WT小鼠更活跃。总之，我们的研究结果表明，作为一种内在的心脏保护因子，TRAF 5通过负调节MEK-ERK 1/2通路在心肌肥厚的发展中起着至关重要的作用。J.细胞。115：349-358，2014. (c)2013 Wiley Periodicals，Inc.
The cytoplasmic signaling protein tumor necrosis factor (TNF) receptor-associated factor 5 (TRAF5), which was identified as a signal transducer for members of the TNF receptor super-family, has been implicated in several biological functions in T/B lymphocytes and the innate immune response against viral infection. However, the role of TRAF5 in cardiac hypertrophy has not been reported. In the present study, we investigated the effect of TRAF5 on the development of pathological cardiac hypertrophy induced by transthoracic aorta constriction (TAC) and further explored the underlying molecular mechanisms. Cardiac hypertrophy and function were evaluated with echocardiography, hemodynamic measurements, pathological and molecular analyses. For the first time, we found that TRAF5 deficiency substantially aggravated cardiac hypertrophy, cardiac dysfunction and fibrosis in response to pressure overload after 4 weeks of TAC compared to wild-type (WT) mice. Moreover, the mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-extracellular signal-regulated kinases 1/2 (ERK1/2) signaling pathway was more activated in TRAF5-deficient mice than WT mice. In conclusion, our results suggest that as an intrinsic cardioprotective factor, TRAF5 plays a crucial role in the development of cardiac hypertrophy through the negative regulation of the MEK-ERK1/2 pathway. J. Cell. Biochem. 115: 349-358, 2014. (c) 2013 Wiley Periodicals, Inc.